In our first WCMR ‘Research in Progress’ meeting of the 2021-22 session, we heard from Dr Conor Lawless who talked about his research project that involves  identifying muscle cells with respiratory chain defects. Read on to find out more.

Muscle weakness is a common symptom in patients with mitochondrial disease.  Although a little painful, it is possible to access patient muscle tissue via biopsy and so it is suitable for detailed patient diagnosis and for research into disease symptoms and progression.

The progression of many kinds of mitochondrial disease is very random (we say the process of progression is ‘stochastic’) and occurs independently in single cells.   As a result, individual muscle fibres, even adjacent fibres, from a single patient can experience extremely diverse effects of disease.  To characterise this diversity, we often investigate muscle tissue at the single cell level.

One class of techniques we use to investigate single cells from muscle tissues involves cutting sections from muscle biopsies, treating the sections, imaging them, identifying individual muscle fibres in the images and classifying the types of biochemical defect in each fibre.  We can try to identify fibres with biochemical defects by comparing them with fibres sampled in the same way from patients without mitochondrial disease.

We have developed several statistical and machine-learning approaches for classifying the type of biochemical defect we find in individual muscle fibres and have found a simple way to improve one method we rely on heavily during both diagnosis and research.  We hope that using it will result in better diagnosis and faster progress towards understanding mitochondrial diseases.